The role of domestic cats in animal-assisted interventions (AAI) has been well- recognized in nursing care for decades, especially improving the quality of life for the elderly, dementia patients, and autistic children. However, despite evidence of efficacy of AAI in calming children and other benefits, the mechanisms of how the human-animal interactions work are unknown, and the specific environmental influences and genetic interactions on human and animal behavior remain unclarified. Many cat breeds are genetically distinct and are selected for different temperaments and "personalities", making individual animals or breeds better or worse for AAI. The genetic mutations affecting monoamine neurotransmitter pathway genes, which encode enzymes that metabolize serotonin and the catecholamines, are under investigation in a host of human and animal studies to understand the genetic components of behavior. Various behaviors, such as boldness, novelty seeking, and aggression have been linked to genetic variation of the genes within these biological pathways in humans, primates, rodents, and dogs. The objective of this R03 request is to investigate the influence of genetic variation in a cat's role in AAI and human-animal interactions. An in-depth, ~10X coverage, genetic sequence of the cat genome has been produced with NHGRI funding, allowing detailed studies of the genetic variation of behavioral genes in the cat. Our central hypothesis is that genetic variations in the feline neurotransmitter pathway genes affect a cat's temperament, making them more or less suitable for AAI and developing positive human-animal interactions. Two specific aims will be conducted. Specific Aim 1: Characterize the genetic variation of behavioral-related genes in cat populations. The principal investigator's previous feline genetic studies at UC Davis have produced an extensive dataset of domestic cat DNA samples, including cats from breeds shown to be more or less conducive for AAI by the UC Davis co-investigators, long-term companion animal behaviorists. Specific Aim 2: Determine the behavioral attributes of a positive feline-human social bond in autistic children. The UC Davis M.I.N.D. Institute has a large study focusing on autism (CHARGE), encompassing ~1300 families that includes information on their pets. A survey will be conducted that will determine the successful attributes of cats that appear to influence the responsiveness and communication of autistic patients. Future studies could associate the genetic variations of patient-owned cats and their effectiveness in AAI, also considering the expression levels of the neurotransmitters of the cats. PUBLIC HEALTH RELEVANCE: These studies will focus on developing survey and genetic tools to help select the most effective cats, or cat breeds, for successful animal-assisted interventions (AAI) for autistic children. Specific cats, whether breeds or individuals, identified from shelter populations, could be selected for potential companions for the autistic child and the specific needs of the families to better facilitate the goals of AAI, potentially improving the quality of life of the patients, the families and the cat. The investigation of neurotransmitter genes in a species with more defined and highly selected behaviors should help decipher these complex pathways, clarifying the process in humans and other species.